Dramatic advances have been made in recent years in the identification and isolation of the hormone receptors and of the cholinergic nicotinic receptor in the electric organ of the electric eel and Torpedo fish. Investigators have even administered purified nicotinic receptor substances from the electric organ of the electric eel into other animals, producing a flaccid paralysis electromyographically and pharmacologically similar to myasthenia gravis, thereby gaining valuable information as to the autoimmune aspects of the neuromuscular disease. Progress in the cholinergic muscarinic receptor field has proceeded at a much slower rate probably due to the lack of a specific and potent muscarinic polypeptide. We have recently found that the muscarinic antagonist 3-quinuclidinyl benzilate (QNB) in a radiolabelled form binds specifically to the pharmacologically relevant muscarinic receptor in the mammalian central nervous system and to the longitudinal muscle of the guinea pig intestine. Because the above muscarinic antagonist may not be binding to the neurotransmitter receptor site, the muscarinic agonist cis-2-methyl, 4-trimethyl-ammoniummethyl, 1,3-dioxolane (cis-dioxolane) in a radiolabelled form will be utilized for the study and characterization of the central muscarinic receptor site. This muscarinic agonist has been recently shown to possess a high affinity for the muscarinic receptors localized in the guinea pig ileum preparation and is unique in that it is not hydrolyzed by acetylcholinesterase. It is our plan to fully characterize and carefully map out the discrete localization of the muscarinic receptors with the muscarinic ligands using biochemical, pharmacological and autoradiographic methods. The determination of the dynamic mechanisms controlling receptor function, synthesis and degradation shall be of great significance in determining whether or not these receptors are involved in brain dysfunction or in the etiology of certain diseases. BIBLIOGRAPHIC REFERENCES: Yamamura, H. I., Manian, A. and Snyder, S. H.: Muscarinic Cholinergic Receptor Binding: Influence of Pimozide and Chlorpromazine Metabolites. Life Sciences. 18: 685-692, 1976. Enna, S. J., Yamamura, H. I., Greenberg, D. and Snyder, S. H.: Development of Muscarinic Cholinergic and GABA Receptor Binding in Chick Embryo Brain. Brain Research. 101: 172-183, 1976.